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![CLL – age at diagnosis. [green segments represent patients over 65 years] [1].](profile/Daniel-Re/publication/281573757/figure/fig1/AS:316654048301056@1452507616883/CLL-age-at-diagnosis-green-segments-represent-patients-over-65-years-1.png)
CLL – age at diagnosis. [green segments represent patients over 65 years] [1].
Source publication
Many advances have been seen in CLL treatment in recent years, primarily benefitting young, fit patients. However, CLL is primarily a disease of the elderly, and many elderly patients currently receive sub-optimal treatment. This is in part due to a lack of consensus surrounding how best to classify their health status. In order to ensure that elde...
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... Rituximab in combination with fludarabine and cyclophosphamide (RFC) is currently the standard of care for medically fit patients with previously untreated chronic lymphocytic leukemia (CLL) [1][2][3]. However, many patients with CLL are in their 70's and beyond before they need to start treatment, and are likely to have a greater co-morbidity burden [4]. For this often medically unfit population, RFC is unsuitable, with data from several clinical studies suggesting that the regimen is associated with excessive toxicity (e.g., ...
... Other therapeutic options are available for unfit patients with CLL and include chlorambucil (Clb) in combination with an anti-CD20 antibody such as rituximab (R-Clb), obinutuzumab (G-Clb) or ofatumumab (O-Clb), rituximab in combination with bendamustine (R-Benda), dose-reduced fludarabine with cyclophosphamide (FC), and a dose-modified RFC regimen (RFC-Lite) [2][3][4][7][8][9][10] [10], and with G-Clb compared with the equivalent rituximab regimen in the CLL11 study (29.2 versus 15.4 months; HR 0.40; 95% CI 0.33-0.50; P\0.001) [11]; however, with a limited number of head-to-head treatment comparisons available, the optimal treatment for unfit patients with CLL remains unclear. ...
Introduction:
Rituximab plus fludarabine and cyclophosphamide (RFC) is the standard of care for fit patients with untreated chronic lymphocytic leukemia (CLL); however, its use is limited in 'unfit' (co-morbid and/or full-dose F-ineligible) patients due to its toxicity profile. We conducted a systematic review and Bayesian network meta-analysis (NMA) to determine the relative efficacy of commercially available interventions for the first-line treatment of unfit CLL patients.
Methods:
For inclusion in the NMA, studies had to be linked via common treatment comparators, report progression-free survival (PFS), and/or overall survival (OS), and meet at least one of the five inclusion criteria: median cumulative illness score >6, median creatinine clearance ≤70 mL/min, existing co-morbidities, median age ≥70 years, and no full-dose F in the comparator arm. A manual review, validated by external experts, of all studies that met at least one of these criteria was also performed to confirm that they evaluated first-line therapeutic options for unfit patients with CLL.
Results:
In unfit patients, the main NMA (five studies for PFS and four for OS) demonstrated clear preference in terms of PFS for obinutuzumab + chlorambucil (G-Clb) versus rituximab + chlorambucil (R-Clb), ofatumumab + chlorambucil (O-Clb), fludarabine and chlorambucil (median hazard ratios [HRs] 0.43, 0.33, 0.20, and 0.19, respectively), and a trend for better efficacy versus rituximab + bendamustine (R-Benda) and RFC-Lite (median HR 0.81 and 0.88, respectively). OS results were generally consistent with PFS data, (median HR 0.48, 0.53, and 0.81, respectively) for G-Clb versus Clb, O-Clb, and R-Clb 0.35 and 0.81 versus F and R-Benda, respectively); however, the OS findings were associated with higher uncertainty. Treatment ranking reflected improved PFS and OS with G-Clb over other treatment strategies (median rank of one for both endpoints).
Conclusion:
G-Clb is likely to show superior efficacy to other treatment options selected in our NMA for unfit treatment-naïve patients with CLL.
Funding:
F. Hoffmann-La Roche Ltd.
